Steroid intermediates



United States Patent '0 2,803,645

Patented Aug. 20, 1957 Compound V is subjected to the following seriesof reactions:' v i I 2,803,645 OH; H3

STEROID INTERMEDIATES 001B, 00:11 5 Harold Hicks Zeiss, New Haven, Conn,assignor to Re- NO NH search Corporation, New York, N. Y., a corporationt 5 ofNew York v NaOI Zn-Hg Heat- No Drawing. Application December 6,1954, l OH 0 3+ Serial No. 473,450 v r p 2 Claims. (Cl.260--468.5) 90020B v C a 602GB I I v VII v 7 OH: I OH: v This invention relates tonew compounds useful in the v 1 production of steroids and to methods ofmaking the same. More particularly, it relates to a new method of 7 NHOH converting the isopropyl group of dehydroabietatic acid 2 and itsS-nitro derivative to an acetyl group. Of particu- HNOZ (CHQZSW I larutility is the methyl ester of 1,12-dimethyl-7-acetyl-8- m0 -0Hnitro-9-keto-A -octahydrophenanthrene 1 carboxylic acld: o s 002011, o0oiorn VIII IX coon; 26 OH; on;

N02 j I.

' OCH: OCH;

0 80012 (1) NaNs 2 Heat H30 COzCHs V 0 100011 01130001 obtained frommethyl S-nitrodehydroabietate by the XI method of the invention. CH3 on,The method briefly comprises the oxidation of dehydroaibietic acidesters and the corresponding 8-nitro derivatives with chromic acid at60-70 C. i CH 1 CH 7 Methyl S-nitrodehydroabietate IV may be made frommethyl dehydroabietate I, through the 6,8-dinitro com- 40 L1A1H4 poundII and 6-amino-8-nitro compound III by the fol- (2) Heat lowing seriesof reactions: 7

N02 0 3 N00 CH3 NHOH3 CH; 0113 CH3 4 XII XIII C CH CH CHs \CH3 a 3 N02H1 OCH; 00H;

03 Benzaldehyde --r NaOH C COQCHZ C CO2CHa I II HI XIV XV on 011 CH 3CH3 3 CH: 3

ca ofi CH; CHa N01 N01 OCHs HNOZ Al-lsopropoxlde J EtOH C .HBCH: XyleneC a COzCHs CQCOzCH:

III IV xvi CH: CH5

/ O CH: OH:

CaH5CH= O= XVI-I XVIII Methyl 6,8-dinitr0dehydroabietate (II) Methyldehydroabietate I g.) is added slowly to a cold mixture (0 C.) of 80 ml.of concentrated sulfuric acid and 40 ml. of concentrated nitric acid.The temperature is kept below 5 C. Considerable heat is evolved and theaddition requires ten hours for completion, after which the mixture ispoured into ice water during stirring. The pale yellow crystals arerecrystallized from ether to give 10 g. (74.4%) of the dinitro ester IIas white needles, M. P. 189-190 C., [ctl +52 (2.5% in 95% ethanol).

Methyl 6-amin0-8-nitrodehydr0abietat (111) The dinitro ester II (4.05g.) in 200 ml. of ethyl acetate and 20 m1. of glacial acetic acid iscatalytically hydrogenated in the presence of platinum oxide, absorbing680 ml. of hydrogen (calcd. 672 ml.). After filtration and evaporationof the solvent, the remaining solid is recrystallized from ethyl acetateto give 3.6 g. (96.2%) of the nitroamino compound III as canary yellowneedles, M. P. 241- 243" C., [011 +102 (1% in 95% ethanol).

Methyl 8-nitradehydroabietate (IV) Methyl 6-amino-8-nitrodehydroabietate III (0.9 g.) is dissolved in 8 ml. of concentrated sulfuric acidat 0 C., to which is added with stirring a cold solution of 0.25 g. ofsodium nitrite in 5 ml. of concentrated sulfuric acid. While maintainingthe solution between 0 and 3 C.,

24 ml. of sirupy phosphoric acid is added with stirring over a period ofone hour. Stirring is continued for twenty minutes at 0 C. and themixture is then poured into 150 ml. of ice and water, giving aprecipitate of the white, crystalline diazonium salt which is filteredand washed with small quantities of cold water. Addition of this salt toethanol produces an evolution of nitrogen with dissolution of the salt.After heating for a short time, the alcoholic solution is concentratedto give flat, light pale yellow plates. Recrystallization of theseplates gives 0.56 g. (65.2%) of the S-nitro ester IV as white plates, M.1I). 192193.5 C.; [ozl +27 (1% in ethano Chromic acid oxidation ofmethyl 8-nitrodehyd0abietate Chromic acid (56 g.) is dissolved in 4 ml.of Water and ml. of glacial acetic acid. The solution is added dropwiseto 3.6 g. of the nitro ester IV in 300 ml. of acetic acid while stirringat 70 C. for ten hours. The acetic acid is distilled off at theaspirator and after pufling the residue, 400 ml. of water, 25 ml. ofconcentrated sulfuric acid and 100 ml. of sulfurous acid is added. Themixture is thoroughly extracted with ether, and the combined etherextracts are washed with Water. The ether layer is then extracted with1% sodium hydroxide soluthe formula -C OCH:

HaC C 02011:!

References Cited in the file of this patent UNITED STATES PATENTS Alt eta1. Apr. 76, 1954 Ritchie Mar. 8, 1955

1. LOWER ALKYL ESTERS OF1,12-DIMETHYL-7-ACETYL-8-NITRO9-KETO-$6,8,13-OCTAHYDROPHENANTHRENE-1-CARBOXYLIC ACID